Usher syndrome
Usher syndrome is a Hörsehbehinderung, which is inherited as an autosomal recessive trait.
In humans, approximately 40 syndromes are known as symptoms include deafness in combination with blindness. Every other affected patients Usher syndrome is the trigger; thus it is the most common cause of hereditary deafness blind.
Signs and symptoms
Defines is Usher syndrome by early-onset sensorineural hearing loss or deafness from birth and later onset of loss of field of vision caused by retinitis pigmentosa (RP, formerly known as " retinitis pigmentosa " means ). The death of the photoreceptors takes place usually from the periphery toward the macula. As is typical for retinitis pigmentosa occurs in the course only to night blindness and then a slow reduction of the visual field to an ever more converging "tunnel vision", which usually depending on Usher subtype leads at a later stage to blindness. The hearing impairment at the Usher syndrome is mainly due to damage to the hair cells in the cochlea of the inner ear. It is usually from birth in the form of numbness or moderate to severe hearing loss.
After the heterogeneous clinical course of Usher syndrome was already described, the Usher syndrome has been divided according to clinical features in three types. After that is a patient with Usher type 1 ( USH1 ), the most severe course of this disease, deaf from birth, and the beginning of retinitis pigmentosa can be diagnosed from the age of 10. In addition, many patients have, but not all, a disorder of balance. When Usher type 2 ( USH2 ) a constant abiding, but severe hearing is established and the beginning of retinitis pigmentosa begins during puberty. Usher type 3 ( USH3 ) differs from USH1 and USH2 by the subsequent insertion of both deafness and the retinitis pigmentosa. The hearing loss is a postlingually and is progressive. The retinitis pigmentosa relies USH3 - patients only in the second half of life. The division into these three types is used as before.
In rare cases, the Usher syndrome is also associated with seizures.
History
Presumably described already in 1858 Albrecht von Graefe, a pioneer of modern ophthalmology, for the first time Usher syndrome. He reported the case of a deaf patient with retinitis pigmentosa who had two affected brothers in the same way.
One of his students, Richard Liebreich, examined a short time later, the population of Berlin on diseases of deafness with retinitis pigmentosa. He has emphasized the recessive nature of this disease, as the cases of blind - deafness combinations particularly in siblings of consanguineous marriages or occurred in families with affected persons in different generations. In addition, his observations provided the first evidence for the coupled inheritance of blindness and deafness, since no cases of isolated blank or numbness could be found in the pedigrees. The disease was eventually named after the British ophthalmologist Charles Usher, who again based on 69 cases out worked the pathology and inheritance of this disease in 1914 ..
Genetics
The genetic heterogeneity was first described in the late 20th century, with the increase of scientific methods. By linkage analyzes of patients several independent loci on different chromosomes have been identified (see Table ) in which hereditary defects that cause the Usher syndrome, have been found. With the aid of these loci, the disease was classified into different subtypes ( USH1A -G, -C USH2A, USH3A -B). By sequencing of candidate genes and the affected gene could be found at most loci. In a subtype Usher - namely USH1A on Chromosomlocus 14q32 - could, however, be shown that this was calculated incorrectly and does not exist, . In contrast, another recently discovered subtype was included with USH2D person affected gene.
Now showed interaction tests ( yeast two -hybrid system, immunoprecipitation, etc.), that the identified gene products are linked together in one or more larger protein complexes from cell adhesion proteins with different connect to the cytoskeleton. These complexes are the one at the synapses and in the charming receiving compartments ( stereocilia of the hair cells, outer segment of the photoreceptors ) locates the affected sensory cells. The available data suggest that these Usher protein complexes occupies a role in the membrane positioning of specific proteins which are probably involved in signal transmission. Missing one of the components, as this protein complex can no longer fulfill its function in the cell and it will probably come to the same degeneration with the known consequences for the patient.
A key role is played here the scaffold protein Harmonin responsible for Usher 1C subtype. This is able to interact with nearly all the hitherto known usher proteins via its so-called PDZ domain. This can Harmonin convey the protein complex. The protein Whirlin described as USH2D has also PDZ domains and could play a similar function.
Dissemination
Epidemiological studies of Usher syndrome show a prevalence of three to six stakeholders, with 100,000 inhabitants at a European in origin population, where Germany is located here at the upper limit. If we take these numbers of patients in addition the age of the person concerned into consideration, an increase in prevalence up to ten sufferers is below 100,000 until the sixth decade of life. The reasons for this are likely to be difficulties in the diagnosis of Usher syndrome, especially in young patients with first onset retinitis pigmentosa only the congenital deafness is often diagnosed. The effective prevalence of Usher syndrome should therefore be higher.
The further classification of patient numbers in the three types of Usher syndrome is uneven. Studies show in Europe accounted for 25 % to 44 % USH1 patients and 56 % to 75% USH2 patients. The same applies to USH3, which was first detected with a very small percentage. But studies show in Birmingham (United Kingdom ) accounted for 20 % and in Finland makes USH3 40 % of cases. Regional founder effects contribute to the large bandwidth, but also the likely diagnosis difficulties distort the results.
Diagnosis and treatment
The earliest possible diagnosis of Usher syndrome is important to reduce the patient the trauma that results from the discovery of this disease, particularly because of the possible consequence of blindness in the already limited hearing. Who is hearing impaired from birth, is part of the risk group within the population. More often only later discovered symptoms which should have a check entails are night blindness, sensitivity to changes in light and a restricted field.
As a diagnostic tool, the electroretinogram to study the function of the retina is capable of onset retinitis pigmentosa an early age to detect. Still in development are DNA - chip and protein chip, which should allow for faster diagnosis of Usher subtype. This may also contribute to the genetic family counseling. Currently this is only the time-consuming way to analyze the individual chromosomes.
For the treatment of retinitis pigmentosa no means exists. Still in the research are gene therapy approaches in which defective genes in the retina could be replaced, or stem cell therapies, in which the degenerated retina to be repaired. In development are also so-called retinal implants, where microsystems technology intended to replace the prosthesis, the functions of the defective retina. Currently intended as a subretinal implant with a possible resolution of 1500 diodes again seer first episode be possible.
Treatment of choice of hearing impairment is the provision of a hearing aid or hearing loss at higher grade with a cochlear implant. Like other people not to be compensated by means of apparatus hearing impairment or the decision that you will not want to run even Usher people under deaf, since the communication is here on the same level with sign language. However, this kind of understanding is only possible with adequate lighting and sufficient distance from the opponent, so that both hands of the opponent are visible. Alternatively, lip-reading are used, but this does usually worse. With increasing blindness there is also the option of either using Lormen or via the so-called tactile sign language (eg Tadoma and Gestuno ) to communicate. In the latter, trying to feel the appropriate gestures, by taking the hands of his opponent during the communication in his own.